A multicenter evaluation of the Technoscreen ADAMTS13 activity semi‐quantitative screening test for thrombotic thrombocytopenic purpura diagnosis and exclusion

Abstract

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal microangiopathy, with an untreated mortality rate of around 90%. TTP is caused by severe deficiency in ADAMTS13, which results in accumulation of ultra large von Willebrand factor multimers, triggering a consumptive thrombocytopenia, microangiopathic hemolytic anemia and end-organ dysfunction and damage. Demonstration of severe ADAMTS13 deficiency is diagnostic for TTP, but long turnaround times for quantitative activity testing often necessitates empirical plasma exchange and/or caplacizumab treatment. Methods: Multisite (n = 4) assessment of the Technoscreen ADAMTS13 activity assay (semi-quantitative flow through screening assay) for diagnosis/exclusion of TTP compared to current standard practice of quantitative assays (ELISA or chemiluminescence AcuStar). Results: A total of 128 patient samples were analyzed, with quantitative ADAMTS13 values ranging from 0% to 150%. The Technoscreen assay demonstrated high sensitivity and negative predictive value (NPV) for ADAMTS13 deficiency, but low specificity and positive predictive value (PPV), especially with one lot of reagent. Good inter-observer reliability was demonstrated. Excluding one possibly compromised batch and other test failures, results of 80 samples yielded sensitivity of 100% (95% CI = 84-100), specificity of 90% (80-95), PPV 77% (58-89) and NPV 100% (93-100). Conclusion:The Technoscreen assay appears to be a reliable screening test for ADAMTS13 activity to exclude TTP in routine clinical practice. However, the assay falsely identified ADAMTS13 deficiency in many cases, partially batch related, which mandates confirmation with a quantitative assay, as well as initial assessment of kits as 'fit for purpose' prior to use for patient testing.

Measuring ADAMTS-13 activity to diagnose thrombotic thrombocytopenic purpura: a novel, fast fiber-optic surface plasmon resonance immunoassay

“…Currently, automated instruments, such as the HemosIL AcuStar and Ceveron s100, are still limitedly present in routine clinical laboratories and discrepant lower ADAMTS-13 activity levels were reported when using the HemosIL AcuStar instrument resulting in false positive TTP diagnosis of alternative patients with TMA [ 15 ]. The rapid Technoscreen assay is also available but is, however, semi-quantitative and potentially less useful to diagnose TTP [ 35 ]. To try to answer the unmet needs of clinical ADAMTS-13 testing for the diagnosis of patients with TTP, this study aimed at developing a fast, easy-to-use diagnostic assay using automated, cost-effective FO-SPR technology to measure ADAMTS-13 activity in real-time.…”